Abstract Adaptation is a fundamental feature of sensory processing whereby recent sensory experience shapes responses to current input. This phenomenon has been observed across species, sensory systems, and stages of processing and has been shown to engage mechanisms that are induced across a range of time-scales from milliseconds to hours. In the visual system, rapid eye and head movements make shorter time-scales of adaptation particularly relevant for determining sensory encoding during ongoing behavior. We have recently identified a form of rapid, stimulus-specific adaptation in the awake mouse primary visual cortex (V1) that is engaged on the scale of milliseconds and persists for seconds. Importantly, adaptation on this time-scale is important for sensory processing as it dramatically impairs performance on an orientation discrimination task. Thus, our goal here is to determine the mechanisms that underlie the magnitude, time-course and stimulus specificity adaptation with the aim of determining how adaptation shapes sensory processing across the visual hierarchy and behavioral states. In particular, we will test the hypothesis that adaptation is largely determined by cortico-cortical short-term synaptic depression and is under the specific control of behavioral context. In Aim 1, we will use intra- and extracellular recordings in combination with opto- and chemogenetic manipulations to determine the contribution of depression at cortico-cortical synapses to adaptation. We will also test the contribution of other mechanisms including activation of intrinsic conductances, recruitment of suppressive mechanisms, and changes in the balance of excitation and inhibition. In Aim 2, we will use extracellular recordings to measure the magnitude, time-course and specificity of adaptation in excitatory and inhibitory neurons in V1 and the higher visual areas. This will reveal how adaptation accumulates along the visual cortical hierarchy, with a particular focus on the ventral stream which is thought to support object recognition through adaptation. In Aim 3, we will investigate the impact of behavioral context on adaptation. Our preliminary data reveal that the specificity of adaptation is different in nave mice and those mice performing an orientation discrimination task. We will determine the specific behavioral contexts (task engagement versus training) that control adaptation, and investigate the circuit mechanisms that support this plasticity. Together, these experiments will reveal how rapid adaptation shapes, and potentially enriches, sensory processing across visual areas and behavioral contexts. We expect that these results will reveal general principles underlying adaptation across sensory areas, as well as mechanisms that are specialized to support visual processing and perception.